Laser Thrombolysis

Laser thrombolysis is an interventional procedure that removes clot
by delivering microsecond pulses via a fluid core catheter. The removal
of the clot results in a restoration of blood flow while maintaining
vascular integrity.

Cardiovascular disease
occurs when arteries and veins become occluded with atherosclerotic
plaque and clot cutting off blood supply to vital organs. This can lead
to potentially fatal conditions such as heart attacks, strokes, and
pulmonary embolism.

To cause injury to tissue with light, the tissue has to absorb the
energy. The amount of energy absorbed by the tissue depends on the
wavelength of the light. The absorption by thrombus is significantly
higher than that by arterial tissue in the visible region of the
electromagnetic spectrum. This allows lasers to selectively remove
thrombus without injuring the vessel wall by using a wavelength in this
region. Current investigations of laser thrombolysis use tunable
pulsed-dye lasers operating in the visible region with pulse lengths of
1-2µs. The absorption of light by the thrombus leads to the explosive
vaporization of part of the clot and the formation of rapidly expanding
and collapsing vapor bubbles. The
dynamics of the vapor bubbles generate pressure transients that disrupt
the clot.

Laser thrombolysis was first used to treat acute myocardial
infarctions caused by thrombosed native coronary arteries that supply
the heart muscles. Preclinical and early clinical studies have
demonstrated effective removal of thrombus and restoration of blood
flow. Pulsed lasers have also been used to remove clots in occluded
bypass grafts and femoral arteries. Recently, there has been
considerable interest in using this technique to remove cerebral clots
in the arteries of the brain. This can be an important step towards the
treatment of stroke that can be caused by occlusions in the brain
arteries.

The use of lasers to
remove tissue was suggested soon after the development of the first
laser in 1960. Some of the clinical applications of lasers to ablate
tissue are bone removal, cartilage smoothing, corneal reshaping, burn
treatment, and laser angioplasty. Laser angioplasty targets the plaque
that is usually present along with clot in diseased arteries. The use of
optical fibers capable of delivering light to previously inaccessible
places in the body has made the medical laser particularly attractive
for many minimally invasive techniques.

The development of a safe and effective laser system for arterial
recanalization is a complex task involving the selection of optimal
laser parameters and delivery of the energy. Early enthusiasm for laser
angioplasty and laser thrombolysis was tempered by unacceptable failure
rates. Some of this was due to poor designs of laser and delivery
systems and a lack of understanding of the ablation mechanism. The last
ten years have seen progress in the design of the system and have
rejuvenated the interest in laser-assisted recanalization techniques.

The broad goal of the research at the Oregon Medical Laser Center is
to make laser thrombolysis a safe and rapid procedure, so that it may be
accepted as a standard treatment modality for vascular disease. Both
basic research into the physical ablation phenomena and clinical trials
are required to achieve this. This thesis addresses some of the
questions regarding the basic physical processes during laser
thrombolysis. With a better understanding of the ablation process, it
may be possible to specify optimal parameters for the design of the
laser and delivery systems.

Vascular disease is the major cause of death and disability in the
United States. More health care dollars are spent on the treatment of
various types of vascular disease than any others. One cause of vessel
disease is the accumulation of plaque and thrombus (clot) in the
arteries resulting in reduction and/or cessation of blood flow to vital
organs. Another related cause is thromboembolism where a piece of a clot
formed elsewhere breaks off and floats downstream blocking blood flow to
a vital organ.

Coronary artery thrombosis resulting in myocardial infarction occurs
in over 1.5 million people in the United States, and over 500,000 will
die as a consequence [fuster 1992, fuster 1992a]. Thrombosis of coronary
artery bypass grafts is the major cause of bypass graft closure at a
rate of about 200,000 cases per year [chesebro 1992]. Thrombosis can
also occur in cerebral arteries and lead to strokes. Over 80% of
strokes are ischemic in nature and are attributed to thrombosis and
embolism [stroke 1995]. Venous thrombosis can lead to pulmonary embolism
where a piece of the clot detaches and embolizes downstream in the lung.

Normally, blood constituents do not interact with intact vascular
endothelium that is a thin layer of cells lining the insides of vessels.
However, the exposure of flowing blood to disrupted vasculature or to
cardiovascular devices initiates complex mechanisms leading to
thrombosis. There is rapid deposition of platelets, insoluble fibrin,
leukocytes, and entrapped erythrocytes [davies 1994]. Clots can also
form when the blood flow slows down as in most cases of venous
thrombosis.

Not all clots are created equal. The etiology and characteristics of
the thrombus, and therefore its preferred treatment modality depend on
where it is formed. Vascular occlusions can occur almost anywhere in the
vascular system including in the coronary arteries, bypass grafts,
cerebro-vasculature, and in the peripheral blood vessels. Arterial flow
conditions give rise to platelet-rich ``white'' thrombi, and static
venous flow yields ``red'' thrombi rich in fibrin and red blood cells.

The mainstay of thrombus management is a regimen of pharmacological
therapy that includes thrombolytics to dissolve the clot and
anticoagulants to prevent clotting. Streptokinase, urokinase, and tPA
are examples of thrombolytics, and heparin is an anticoagulant. The use
of these drugs has been shown to improve cardiac function [debono 1992,
gusto 1993]. Alternate approaches to vascular recanalization are balloon
angioplasty, rotoblader atherectomy, and aspiration devices [goudreau
1991, ivanhoe 1992, rosenblum 1992, grines 1992]. In balloon angioplasty
a balloon is inflated inside the vessel to mechanically re-mold the
lumen. When all else fails or if the thrombus burden is too large,
bypass surgery may be performed.

Acute coronary thrombosis is common to the pathogenesis of
myocardial infarction and of unstable angina. Fissuring or rupture of an
atherosclerotic plaque plays a fundamental role in the formation of
coronary artery thrombosis [badimon 1992]. When the injury to the vessel
is mild, the thrombogenic stimulus is relatively limited, and the
resulting occlusion is transient as in unstable angina. The endothelium
is denuded with thrombi adherent to the surface of the plaque. Deep
vessel injury results in persistent thrombotic occlusion and myocardial
infarction. Major plaque disruption exposes the lipid core to the lumen.
Blood enters the core and thrombus forms within the plaque expanding its
volume rapidly. The intraplaque component of the thrombus is very rich
in platelets. The intraluminal part forms as the last stage of the
occlusion and is rich in fibrin and red cells.

Thrombolytic therapy with pharmacological agents is paramount in
myocardial infarction, but it is less effective in unstable angina
[debono 1994]. The reduction in mortality associated with the use of
thrombolytic agents is impressive [isis 1992, gusto 1993]. The most
feared complication of thrombolytic therapy is intracranial hemorrhage
since fatality rates in such cases can range from 44% to 75% [gore
1995]. Some patients have contra-indications to the drugs and cannot
receive them due to bleeding disorders, recent strokes, etc. Also, the
thrombus burden is usually not removed completely. Residual thrombus is
very thrombogenic acting as substrate for additional clot formation.
Re-occlusion of the artery is therefore a problem.

Percutaneous interventional techniques like balloon angioplasty and
atherectomy were initially used as a secondary treatment to keep the
vessel open after thrombolytic therapy. Angioplasty has now evolved as a
primary intervention for patients who have shown contra-indications to
thrombolytics. Acute results of balloon angioplasty are promising with a
relatively low rate of abrupt vessel closure (~5%) [linkoff 1992].
Drawbacks, however, appear in the short-term follow-up phases where
vessel closure rates of 30-50% within six months have been reported
[ellis 1989, hirshfeld 1991]. This has been largely attributed to the
damage incurred by the vessel wall during inflation of the balloon.

The last line of defense is bypass surgery where a piece of a vein
from the leg is grafted around the occlusion to re-establish blood flow.
This is an open chest procedure and involves severe trauma to the
patient. There is also an increased risk of re-occlusion due to
thrombosis of the vein graft.

The term ``stroke'' is used to describe a number of
brain disorders with a common feature of a defect in the cerebral
vasculature. Strokes are classified according to whether they are
ischemic or hemorrhagic. Most strokes are due to arterial occlusion with
brain ischemia (oxygen deprivation) leading to cerebral infarction or
transient ischemic attacks [stroke 1995].

Similar to the pathogenesis of acute coronary syndromes, thrombosis
over a disrupted plaque can play a key role in cerebrovascular
occlusions [badimon 1992]. However, intracranial hemorrhage and embolism
may also be involved; common sources for the thrombus embolus are the
heart and the carotid arteries. Transient ischemic attacks result from
progressive narrowing of the vessel leading to reduction of blood flow
or from a transient occlusion by a thrombus. Cerebral infarction arises
from total occlusions.

Early studies of therapies for acute stroke show benefit at a high
price [langhorne 1994]. It is clear that cerebral perfusion has to be
re-established within 3-6 hours to restore normal neurological
function. The treatment is to infuse the patient with thrombolytics and
agents that dissolve thrombus and increase cerebral perfusion. This
treatment modality is not always successful, and sometimes the occlusion
is not cleared in time. The thrombolytic tPA has recently been approved
by the Food and Drug Administration for the treatment of embolic stroke.
Mechanical intervention has not been tried on large scale due to
difficult access to the occlusion via the tortuous bends in the
arteries. Also, the arteries of the brain are more fragile, increasing
the risk of vascular injury and vasospasm. A major problem in the
treatment of stroke is the recurrence of stroke. This is particularly
true of strokes that are embolic in nature. In such cases the underlying
cause of the stroke has to be treated where possible.

Claudication is the clinical term for pain in the
muscles of the leg due to insufficient delivery of oxygen resulting from
a proximal obstruction to blood flow. Peripheral arterial disease is
frequently asymptomatic for long periods and often occurs together with
coronary artery disease. The risk of a leg amputation is relatively low
(~5%); however, life expectancy is generally reduced [verhaeghe
1992]. A large number of patients die of cardiovascular causes.

Smokers demonstrate a higher incidence of fibrous, calcified, and
ulcerated plaques in the aorta and in the iliofemoral circulation
[badimon 1992]. Diabetes is also commonly associated with disease of the
iliofemoral and distal arteries of the leg. Major acute arterial
occlusion is often due to fibrin-rich emboli arising from the heart or
occasionally from venous thromboembolism through a patent foramen ovale
(an abnormal communication between chambers in the heart). Microemboli
causing digital infarction may arise from cardiac sources or from
fragmentation of a proximal thrombus during vascular intervention.

In most patients with intermittent claudication, conservative
therapy is usually lifestyle advice to exercise regularly and to reduce
smoking. In acute cases the primary treatments are reconstructive
surgery and catheter recanalization procedures. Arterial bypass grafts
and percutaneous transluminal angioplasty are the most common procedures
performed [wholey 1993]. Systemic thrombolysis with drugs has a low
success rate and a significant risk of bleeding. Local thrombolysis
delivers drugs via a catheter and has a higher success rate.
Nevertheless, the use of thrombolytics is frequently not the treatment
of choice for peripheral arterial disease.

Bypass surgery is generally performed for diffuse atherosclerotic
disease resulting from a chronic build-up or when there has already been
a previous intervention. It is also done when arterial disease develops
at multiple sites. Basically, a piece of the saphenous vein in the leg
is grafted and implanted to bypass the occlusion.

A problem plaguing bypass surgery is thrombosis of the vein graft
cutting off blood flow again. Disease of vein grafts is a form of
accelerated atherosclerosis that begins with acute vascular injury,
mural thrombosis, and proliferation of smooth muscle cells in the vessel
wall. Injury to the vein graft results from procurement of the vein from
the leg, surgical handling, delays before insertion, and from the
increased shear forces of the pulsatile arterial system. There is
platelet deposition and secretion of growth factors for smooth muscle
cells and white cells. Recent bypass procedures have used a graft from
the internal mammary artery that is more protected from generalized
injury and platelet deposition. This is probably due to previous
adaption to arterial shear forces.

There is no satisfactory treatment for thrombosed vein grafts.
Mechanical intervention like angioplasty is not preferred because of
problems and embolization at lesions to distal coronary arteries
[defeyter 1988}. Thrombolytics ease the thrombus burden in about 50% of
the cases, but the re-occlusion rate is around 30% [chesebro 1992,
gavaghan 1991]. Because platelet deposition starts as soon as blood
flows through the vein graft, perioperative antithrombotic therapy is
critical.

Deep vein thrombosis is a common and potentially dangerous
complication of a primary illness in hospitalized patients. It may lead
to pulmonary embolism that can be fatal. When venous thrombi dislodge,
they can reach the pulmonary arterial circulation and may adhere to the
bifurcation of the pulmonary artery. The thrombus generally forms in
post-operative patients who are under extensive bed rest. It is also
common in people who spend extended periods of time in a sedentary
position.

Venous thrombosis develops when stasis in the deep veins of the legs
occurs at times of increased coagulability of the blood [badimon 1992].
This combination leads to local generation of thrombin that is the
crucial event in the pathogenesis of the disease. Since the clot forms
under static conditions of blood flow more red blood cells are trapped
and the clot appears red. Vessel wall injury is less likely to be
involved. Deep vein thrombosis can also go undetected for some time, and
they can be several weeks old before turning symptomatic.

Prevention of deep vein thrombosis is a critical part of
post-operative care. This involves elimination of stasis and fighting
blood coagulation. Although anticoagulant therapy is highly effective,
two thirds of the patients who die from pulmonary embolism succumb
abruptly or before the therapy can take effect. Thrombolytic therapy is
generally more rapid than anticoagulants in thrombus removal.
Contra-indications again appear in the form of bleeding.

Surgical intervention for venous thrombosis consists of either
thrombectomy or venous interruption. The role of thrombectomy remains
controversial. There are several techniques for the interruption of the
inferior vena cava that is the main blood vessel carrying blood from the
legs back to the heart. One example is a variety of external clips
designed to partially compress the vein so that emboli floating in the
stream are filtered [kakkar 1994]. However, compromised cardiac output
due to inadequate venous return led to low acceptance of these
techniques in clinical practice.

The disadvantages of current techniques to rapidly clear large
thrombus burden in occluded arteries led to the search for an
alternative method that did not endanger the vessel wall. The potential
for laser energy to remove atherosclerotic obstructions (plaque) was
described as early as 1963 [mcguff 1963]. Since then most investigations
have concentrated on the removal of plaque in a technique called laser
angioplasty [grundfest 1985}. In 1983 Lee et al. used an argon
laser to vaporize human thrombus in vitro [lee 1983]. If the
arterial occlusions is a combination of plaque and thrombus, it is
essential to remove both for effective therapy.

Early studies of both laser angioplasty and laser
thrombolysis used continuous wave laser to remove the arterial
obstruction. Crea and Abela attempted to recanalize thrombosed coronary
arteries in dogs using an argon ion laser [crea 1985}. The wavelengths
used were 488nm and 514nm, and the laser energy was transmitted via
140 or 200µm cleaved silica fibers. The results were not
encouraging with recanalization reported in only 1 of 19 dogs.
Perforation of the arterial lumen was observed in 7 of 9 dogs. Minimal
thrombus was removed and there was evidence of charring at the laser
delivery sites.

The results of several subsequent studies have demonstrated the
limitations of both continuous laser energy and delivery by hard silica
fibers [choy 1982, choy 1984, abela 1982, abela 1985]. Irradiation by a
continuous wave laser does not confine the heat produced to the target
area. The diffusion of heat out of the target area can result in thermal
necrosis and even charring in the surrounding tissue. These factors also
lead to intense vasospasm and thrombosis [ginsberg 1985]. It has been
reported recently that accelerated intimal hyperplasia can be attributed
to thermal injury [douek 1992]. Intimal hyperplasia is a condition where
the smooth muscle cells in the vessel wall proliferate and cause closure
of the vessel.

Bare silica fibers are generally stiff and have sharp edges.
Tortuous bends in the vascular system are difficult to navigate and
therefore limit access to the occlusion. The sharp edges of the fiber
pose considerable hazards to the vessel wall, and arterial perforations
and fracture of fibers have been reported in animal trials. The fiber
tip was then covered with a metal cap (``hot-tip'') in an attempt to
reduce the sharp profile of the fiber [hussein 1986, welch 1987a,
lecarpentier 1988, labs 1991, tomaru 1992b]. While results from animal
trials were promising, an unacceptable number of thermal injuries during
angioplasty in human coronary arteries were reported. Consequently, most
attempts at laser angioplasty and thrombolysis using continuous-wave
lasers were abandoned.

Srinivasan et al. reported their experience using
ultrashort excimer laser pulses to produce precise cuts in polymers
without adjacent thermal effects [srinivasan 1982]. This approach of
using pulsed lasers to limit thermal effects can also be be used to
ablate tissue. The limiting pulse length would be determined by the
thermal relaxation time of the material. This is the time for heat to
diffuse out of the irradiated volume and is determined by the thermal
diffusivity of the tissue and the dimensions of the volume. When laser
energy is deposited in pulses shorter than the thermal relaxation time,
heat accumulates and high temperatures are achieved. The ablative event
can then occur before the heat diffuses out of irradiated volume. This
confinement of heat can reduce the thermal damage incurred by adjacent
tissue [jacques 1993b, jacques 1993].

For vascular structures the thermal relaxation time is of the order
of milliseconds, so lasers with pulse durations less than 1ms are
likely to produce little thermal injury [linsker 1984, anderson 1983].
Pulsed lasers from the ultraviolet [grundfest 1985a, isner 1985, pettit
1993, deckelbaum 1985, litvack 1990], visible [prince 1986, prince
1986a, lamuraglia 1988b, lamuraglia 1990, gregory 1990a, gregory 1994],
and infrared [kopchok 1990, geschwind 1991, knopf 1992] have been
investigated for both angioplasty and thrombolysis. Notable among these
are the excimer (308nm, 351nm, 100-200ns), tunable pulsed-dye
(400-600nm, 1µs), and the Ho:YAG (2.1µm, 250µs) lasers. The
excimer and holmium lasers are popular because of the potential for a
single laser system to treat both plaque and thrombus. The excimer laser
targets the tissue proteins, while the holmium energy is absorbed by
tissue water. Both these chromophores are present in both plaque and
thrombus.

Excimer nm light in 100-200ns pulses are being tested for thrombus
removal in animal and clinical trials [pettit 1993]. These systems were
designed for and have had extensive evaluation for the treatment of
atherosclerotic obstructions.

The laser energy is delivered via a catheter made of bundles of
50-100µm core diameter fused silica fibers circumferentially
arranged around a central guidewire lumen. Conventional angioplasty
guidewires are pushed through the thrombus into the distal part of the
vessel. The laser catheter is brought over the guidewire to the
thrombus, and pulse energies of 40-50mJ/sq mm are delivered at a
repetition rate of 10-30Hz. Balloon angioplasty immediately after the
laser procedure is generally required to open the vessel further.

Ultraviolet light of 308nm is strongly absorbed by the tissue
protein in the clot; the depth of penetration is about 30µm. This
would theoretically allow for precise etching of clot similar to that
demonstrated in atherosclerotic tissue and polymers. However, the
results have been conflicting [rosenfield 1992, estella 1992]. The
clinical excimer laser is configured to principally treat plaque.
Refining the laser and delivery systems, technique, and case selection
specifically for treatment of thrombi may improve the efficacy of the
excimer laser for thrombolysis. However, ultraviolet photons have
sufficient energy to break certain carbon bonds and may result in
unwanted photochemical reactions.

One feature that was noted was that the ablative event was different
from previous continuous-wave ablation studies. Ablation was initiated
by explosive vaporization of the tissue and the subsequent formation of
a vapor bubble. The dynamics of this rapidly expanding and collapsing
bubble exert mechanical forces on the clot leading to removal of more
clot. This bubble formation occurs almost always when tissue is ablated
under a liquid with a pulsed laser. The removal of thrombus under these
conditions is usually more efficient but less controlled.

Holmium/thulium:YAG lasers emitting 2.1µm radiation have been
successfully used for angioplasty and are now being tested for
thrombolysis [kopchok 1990]. Other applications include cutting bone and
intervertebral discs. The pulse duration is 250µs in the free
running mode and 1µs in a Q-switched mode. Water has an absorption
peak at 2.1µm, and the penetration depth of the holmium radiation
in water-containing tissues is about 300µm.

The holmium laser is a solid state device and is favored for its
smaller size and ease of operation. The clinical laser for angioplasty
and thrombolysis is configured to emit 250µs pulses. The energy is
delivered to coronary artery thrombi via a catheter similar in design to
the one for the excimer laser. The catheter is 1.4-1.7mm in diameter
and delivers 250-600mJ pulses at a repetition rate of 5Hz.

The results of holmium laser thrombolysis are fair. In one study the
majority of the thrombus was cleared and the residual stenosis was less
than 30% in all cases [topaz 1993]. No acute adverse procedural
complications were reported. However, balloon angioplasty was still
required as a follow-up procedure.

There is some reservation regarding the holmium laser for
thrombolysis. Stress wave effects and the formation of vapor bubbles
have been shown to induce damage to adjacent tissue [delatorre 1992a].
Hassenstein et al. reported formation of thrombotic occlusions during
holmium laser angioplasty [hassenstein 1991]. Another potential
disadvantage is the inability of the holmium laser to selectively target
thrombus without ablating the vessel wall. Since water is present in
roughly the same proportions in all tissues, the holmium laser does not
discriminate between an arterial occlusion and healthy vessel wall. This
presents the danger of perforations caused by inadvertent ablation of
arterial tissue.

A laser system capable of selectively targeting the thrombus is
therefore desirable. This capability is offered by lasers emitting in
the ultraviolet and visible regions, where the absorption by thrombus is
much higher than that by artery. The principal chromophore of thrombus
in the visible waveband is hemoglobin present in the red blood cells.
Since higher absorption coefficients require less energy per unit area
to achieve ablation, the ablation threshold for artery is higher than
that for clot. Pulsed lasers operating in this waveband at radiant
exposures between the thresholds for artery and clot can therefore
selectively remove clot.

Prince et al. reported that differential absorption of light of
selected wavelengths between plaque and arterial wall resulted in
differences in ablation thresholds [prince 1985a, prince 1985b, prince
1986}. LaMuraglia et al. conducted spectrophotometric studies to
determine the absorption spectra of thrombus and normal arterial tissue
in the 400-600nm waveband [lamuraglia 1990]. An increase in absorption
of nearly two orders of magnitude between clot and artery due to the
presence of hemoglobin was observed.

Based on these tissue spectrophotometric studies, a pulsed-dye laser
system was developed. The wavelength of emission is tunable between
400-600nm, and the pulse duration is 1-2µs. A longer pulse could
potentially work as long as it stayed below the thermal relaxation time
of tissue (~1ms). The lasers currently configured in clinical
settings operate at 480nm with pulse widths of 1-2µs [gregory 1994,
lamuraglia 1988a]. The ablation thresholds for acute arterial thrombus
and normal arterial tissue measured with this laser in vivo and in vitro
were approximately 15mJ/sq.mm and 1500mJ/sq.mm respectively [gregory 1989,
gregory 1990a].

Light delivery is achieved with a fluid-core light guide, that is
essentially a tubing of low refractive
index filled with an optically transparent fluid of higher refractive
index [gregory 1989, gregory 1990b]. Light propagation is similar to
that of a regular optical fiber. The light is launched from the laser
into an optical fiber contained within the fluid catheter. The fiber in
turn launches the light into the optical fluid that finally delivers it
to the target. Further, the catheter is open-ended at the distal end
allowing the fluid to flow out of the catheter. The advantages over
delivery by regular optical fibers are:

increased flexibility and reduced risk of perforations because of
the soft material of the tubing;

removal of blood and ablation debris by the flowing fluid to clear
the path for laser delivery to the thrombus;

contact with the target is not necessary because light can be
transmitted past the end of the catheter, and this feature may reduce
mechanical injury to the vessel wall;

the optical fluid used is radiographic contrast used in
conventional angiography. Being radio-opaque, contrast gives the
additional capability of monitoring laser thrombolysis progress in real
time using fluoroscopy.

The laser catheter is fitted with a Y-adapter. The optical fiber is
inserted into the catheter tubing through one leg of the adapter. The
distal end of the fiber is kept about 20cm from the distal part of the
catheter. A fluid injector injects the contrast media through the other
leg of the Y-adapter. The catheter can be inserted into the femoral
artery in the leg and advanced to the occlusion in the coronary artery
over a monorail guidewire.

The initial pulse energy at the output end of the fiber is
approximately 80mJ. The transmission through the optically clear fluid
is about 75% resulting in an output energy of 60mJ. The internal
diameter of the optical channel is 1.1mm that results in a laser spot
diameter of similar dimensions. The pulse repetition rate is 3Hz. The
fluid injector maintains the contrast flow between 0.3-0.5ml/sec
that provides adequate light transmission up to 1cm from the tip of the
catheter. The tip of the catheter is marked with a gold band for
visualization during fluoroscopy.

The pulsed-dye laser thrombolysis technique was tested on a canine
model with promising results [gregory 1989]. Coronary artery thrombi
were removed in all of 22 dogs without perforation, vasospasm, or other
untoward incidents. All thrombi were removed within 600 pulses. The
patency rate of the vessels 90 minutes after the procedure was 80%.

Based on these favorable animal studies of laser thrombolysis and
approval from the Food and Drug Administration, a pilot study of laser
thrombolysis in acute myocardial infarction in humans was performed. The
criteria for patient selection was contra-indications to or failure of
thrombolytic drugs. The procedures were performed at St. Vincent
Hospital, Portland, Oregon and at St. Joseph's Hospital, Atlanta,
Georgia. Effective thrombus removal was demonstrated in 16 of 18
patients [gregoryclinical].